Transcriptional Regulation During Oxidative Stress

Colorado State University, Fort Collins CO

Investigators

Abstract

Project Abstract: This project directly addresses the fundamental biological question as to how genes are turned on and off in response to an environmental stimulus. Yeast is used as the model system and the response to oxidative stress as the stimulus. The yeast system allows for the identification and characterization of important players in living cells (in vivo), followed by expansion and refinement of these studies at the mechanistic level (in vitro). This multidisciplinary approach involving genetic, molecular, and biochemical techniques provides research opportunities for students at various skill levels. In addition, the oxidative stress response is a critical physiological response that is extremely important to cell survival in an oxygen-rich environment. Indeed, oxidative stress is also highly relevant to the human condition because it plays fundamental roles in aging, neurodegenerative diseases, and cancer. With the goal of understanding transcriptional themes in response to oxidative stress, this project explores two main areas: the role of regulatory factors in the response to oxidative stress and the mechanism(s) by which a single activator can differentially regulate a wide array of genes. Taken together, these combined studies will advance the understanding of the transcriptional response to oxidative stress, and will add to the current knowledge of the ways in which genes are turned on and off in response to an environmental change. In addition to the intellectual merit, the project will have broad impact in at least four ways. First, many aspects of these studies will provide suitable projects for undergraduate trainees, who may have time constraints as well as limited laboratory experience. Second, studies with higher technical and time demands will provide outstanding cross-training experiences for graduate students in a number of different disciplines (biochemistry, genetics, molecular biology). It is important to note that a majority of these techniques are versatile. Trainees could certainly utilize these techniques to investigate other critical genetic mechanisms (DNA repair, replication, recombination, RNA metabolism, epigentics, etc.) in their future careers. Third, to propagate the tradition of outreach, both undergraduate and graduate students will be involved in taking gene expression studies into elementary school classrooms. Fourth, results from this project will be published in broad based scientific journals, and presented at local and international meetings. Taken together, this project directly supports the mission of the NSF to advance discovery and understanding, while promoting teaching, training and learning.